Overwhelming evidence indicates that excess exposure to the sun's ultraviolet (UV) radiation suppresses the immune responses, which can promote tumor growth and the risk of skin cancer. Exposure to UV radiation also causes a variety of histological responses in skin including an increase in elastic fibers replacing the collagen in the dermal matrix, an increase in glycosaminoglycans, collagen cross-linking, and epidermal thickening. These processes begin when natural chromophores in skin absorb solar radiation. This proposal describes a research program directed at studying the photoreactivity of two epidermal chromophores urocanic acid and melanin. The specific goals of the project are (a) to measure the in vitro action spectrum for the generation of singlet molecular oxygen following the excitation of trans-urocanic acid and to determine if this measured action spectrum quantitatively agrees with any of the reported in vivo action spectra for various histological responses of skin to UV exposure, (b) to develop a comprehensive model for the spectroscopy and wavelength-dependent photoreactivity of cis- urocanic acid and to determine action spectra for its various photochemical processes, (c) to develop a comprehensive model for the spectroscopy and photochemistry of synthetic and natural melanins, and (d) to study how drug molecules bound to melanin affect the photodynamics of both the drug and pigment.